The objectives of this research program are to understand the structural and functional aspects of macromolecules at crucial interfaces in biochemistry. Efforts are divided into three principal areas: 1) DNA-protein interactions; substructures of eukaryotic chromosomes and histone-DNA interacton. Principal objective is to determine the number of, and sequence specificity if any, for binding DNA duplex by histone proteins. Intermediates in replication of T7 bacteriophage, and supercoil transitions in PMZ2 DNA are being analyzed by fiber diffraction and electron microscope image reconstitution, as simpler models of DNA packaging. 2) Membrane bound proteins; the nurochemical acetyl choline receptor from electric fish and its organization in end-plate membranes is being studied by x-ray diffraction and electron microscopy. The single crystal structure of alpha-Bungarotoxin is being solved to contribute to understanding of its mechanism in blocking the end-plate receptor. Suitable crystals and diffraction patterns have been obtained in our laboratory. 3) Enzymes- -structure and function: the high resolution structure of trypsin and inhibited derivatives have been solved. The trypsinogen structure analysis is nearing completion and should help to understand the mechanism of zymogen activation, not only in trypsin, but in plasmin, thrombin and other physiologically important serine proteases. High resolution crystal structure of thymidylate synthetase is also in preliminary stages.